Gemcitabine +/- Imatinib Mesylate, Patients w/Previously Treated Metastatic Breast Cancer

OBJECTIVES:

Primary

- Compare time to progression in patients with previously treated locally advanced or
metastatic breast cancer treated with gemcitabine hydrochloride with vs without imatinib
mesylate.

Secondary

- Compare the efficacy of these regimens in these patients.

- Compare the overall survival of patients treated with these regimens.

- Compare the safety and tolerability of these regimens in these patients.

OUTLINE: This is a multicenter, open-label, randomized study. Patients are randomized to 1 of
2 treatment arms.

- Arm I: Patients receive gemcitabine hydrochloride IV on days 3 and 10.

- Arm II: Patients receive gemcitabine hydrochloride IV on days 3 and 10 and oral imatinib
mesylate once daily on days 1-5 and 8-12.

In both arms, treatment repeats every 21 days in the absence of disease progression or
unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

- Histologically confirmed breast cancer

- Locally advanced or metastatic disease

- Disease progression after at least 1 prior chemotherapy regimen for metastatic
disease

- No more than 2 prior chemotherapy regimens for metastatic disease (prior
neoadjuvant or adjuvant treatment will not be included in determining the
number of prior chemotherapy regimens)

- Measurable disease

- No known symptomatic or untreated brain metastases or carcinomatous meningitis

- Previously treated and clinically stable brain metastases allowed provided
patient has been off steroids for > 7 days

- Hormone receptor status not specified

PATIENT CHARACTERISTICS:

- Male or female

- Menopausal status not specified

- ECOG performance status 0-2

- Life expectancy ≥ 3 months

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Bilirubin ≤ 1.5 times upper limit of normal (ULN)

- AST or ALT ≤ 2.5 times ULN

- Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 3 months after
completion of study therapy

- Able to swallow oral medication

- No coexisting medical condition that would preclude study compliance

- No uncontrolled illness, including any of the following:

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia requiring therapy

- Myocardial infarction within the past 6 months

- Active infection

- No New York Heart Association class III-IV cardiac disease

- No history of allergic reaction attributed to compounds of similar chemical or
biologic composition to gemcitabine hydrochloride and/or imatinib mesylate

- No other primary malignancies within the past 5 years except for carcinoma in situ of
the cervix or nonmelanoma skin cancer

- No known chronic liver disease (i.e., chronic active hepatitis or cirrhosis)

- No known HIV infection

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- Recovered from all prior therapy

- More than 2 weeks since prior surgery

- At least 2 weeks since prior hormonal therapy

- At least 2 weeks since prior trastuzumab (Herceptin®)

- At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas)

- At least 3 weeks since prior anti-vascular endothelial growth factor therapy

- More than 28 days since prior investigational agents

- At least 3 weeks since prior radiotherapy

- Must have evidence of ≥ 1 measurable target lesion outside the irradiated fields
OR radiologically confirmed disease progression within the irradiated fields
after completion of radiotherapy

- No prior imatinib mesylate for metastatic disease

- No prior gemcitabine hydrochloride for metastatic disease

- More than 6 months since prior adjuvant gemcitabine hydrochloride

- No other concurrent investigational or commercial agents

- No concurrent therapeutic anticoagulation with warfarin (e.g., Coumadin® or
Coumadine®)

- Concurrent heparin or low-molecular weight heparin (e.g., Lovenox®) for
therapeutic anticoagulation allowed

- Concurrent prophylactic warfarin therapy (e.g., mini-dose Coumadin® ≤ 1 mg daily)
to maintain catheter patency allowed

- No concurrent routine chronic systemic corticosteroids

- No concurrent medications that would preclude study compliance